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Ipf or non ipf interstitial lung diseases


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Ipf or non ipf interstitial lung diseases

  1. 1. IPF or Non-IPF Interstitial Lung Diseases By Gamal Rabie Agmy , MD , FCCP Professor of Chest Diseases ,Assiut University
  2. 2. What is the Pulmonary Interstitium? • Interstitial compartment is the portion of the lung sandwiched between the epithelial and endothelial basement membrane • Expansion of the interstitial compartment by inflammation with or without fibrosis – Necrosis – Hyperplasia – Collapse of basement membrane – Inflammatory cells
  3. 3. The Lung Interstitium The interstitium of the lung is not normally visible radiographically; it becomes visible only when disease (e.g., edema, fibrosis, tumor) increases its volume and attenuation. The interstitial space is defined as continuum of loose connective tissue throughout the lung composed of three subdivisions: (i) the bronchovascular (axial), surrounding the bronchi, arteries, and veins from the lung root to the level of the respiratory bronchiole (ii) the parenchymal (acinar), situated between the alveolar and capillary basement membranes (iii) the subpleural, situated beneath the pleura, as well as in the interlobular septae.
  4. 4. Secondary pulmonary lobular anatomy
  5. 5. The terminal bronchiole in the center divides into respiratory bronchioles with acini that contain alveoli. Lymphatics and veins run within the interlobular septa Centrilobular area in blue (left) and perilymphatic area in yellow (right)
  6. 6. Ideal ILD doctor Pulmonologist Radiologist Pathologist
  7. 7. Diffuse Parenchymal Lung Disease DPLD of known cause (e.g. drugs, dust exposure, collagen vascular disease) Idiopathic Granulomatous interstitial DPLD (e.g. pneumonias sarcoidosis) Idiopathic pulmonary fibrosis (IPF) Other forms of DPLD (e.g. LAM, HX, eosin. pneum. etc.) IIP other than idiopathic pulmonary fibrosis Desquamative interstitial pneumonia (DIP) Respiratory bronchiolitis/ Interst. lung dis. (RBILD) Acute interstitial pneumonia (AIP) Cryptogenic organising pneumonia (COP) Nonspecific interstitial pneumonia (NSIP) Lymphocytic interstitial pneumonia (LIP)
  8. 8. Clinical Categorisation of Idiopathic Interstitial Pneumonias
  9. 9. 7 histological categories • • • • • • • Usual interstitial pneumonia (UIP) Nonspecific interstitial pneumonia (NSIP) Organising pneumonia (OP)* Diffuse alveolar damage (DAD) Desquamative interstitial pneumonia (DIP)** Respiratory bronchiolitis (RB) Lymphocytic interstitial pneumonia (LIP) * previously BOOP ** previously AMP
  10. 10. Correlation with HRCT patterns UIP + NSIP + OP + DAD + DIP + RB + LIP + = IPF = NSIP = COP = AIP = DIP = RB-ILD = LIP  7 clinical-radiological-pathological categories ATS/ERS International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias, AJRCCM Vol 165. pp 277-304, 2002
  11. 11. IPF/UIP „disease status‟ Histology: • Heterogeneous appearance ü(hardly any inflammation) • Temporal heterogeneity Old + new fibrosis (fibroblastic foci)
  12. 12. Non-specific interstitial pneumonia ’IIP-NSIP cellular / fibrotic variant’ • fine reticulation • ground glass • temporal uniformity on biopsy • no / few fibroblastic foci
  13. 13. Cryptogenic organising pneumonia (BOOP) • patchy consolidations (95%) • perilobular opacity (50%) Ujita, Radiology 2004; 232: 757-61
  14. 14. Acute interstitial pneumonia Congestion & oedema Exudative phase acute onset, with systemic features: idiopathic ARDS  granulocytes + occasional lymphocytes; debris  survival from diagnosis often days despite mechanical support 
  15. 15. Respiratory bronchiolitis associated interstitial lung disease cigarette smoker  obstructive or restrictive lung function  AM with smoker’s inclusions on BAL 
  16. 16. Desquamative interstitial pneumonia (AMP)   smoker BAL: AM+++N+E+L
  17. 17. LIP Lymphocytic interstitial pneumonia AIDS  lymphoproliferative  rheumatological  idiopathic (rare)  lymphocytes on BAL 
  18. 18. Radiologist Pulmonologist Diagnosis Pathologist Correct IIP diagnoses need teamwork and experience Flaherty KR, AJRCCM 2004;170:904-10
  19. 19. Practical issues • Clinical setting with regular meetings of key specialists • Not all IIP cases are classifiable: „non-classifiable interstitial pneumonias‟ (8th category) • NSIP is an area of important uncertainty (NSIP ~ provisional category) > 50% of inter-observer variation between pathologists and radiologists relate to the diagnosis of NSIP Nicholson AG, Thorax 2004; 59:500-5 // Aziz ZA, Thorax 2004; 59:506-11
  20. 20. ATS/ERS INTERNATIONAL MULTIDISCIPLINARY CONSENSUS CLASSIFICATION OF IDIOPATHIC INTERSTITIAL PNEUMONIAS General Principles and Recommendations Co-chairs: William D. Travis, M.D. Talmadge King, Jr. M.D. Am J Respir Crit Care Med 2002; 165: 277
  21. 21. Classification
  22. 22. Diagnostic Approach According to ATS/ERS Statement 2002
  23. 23. Roles of Clinicians, Radiologists and Pathologists •History •Exposure •Drugs •Symptoms & Signs Clinicians (Pulmonologists) Radiologists •Should know, identify and report patternspecific features •Systemic Diseases (CVD) •Age Pathologists •Should know, identify and report patternspecific features
  24. 24. Diagnostic Process in DPLD History, physical examination, chest radiograph, lung function tests Not IIP Possible IIP e.g. assoc. collagen vascular disease, environmental, drug-related, etc. HRCT
  25. 25. History: Onset of Pulmonary Symptoms ACUTE SUBACUTE CHRONIC • COP • COP • IPF • AIP • Subacute HP • NSIP • Ac.Eos.Pn. • Chron.Eos.Pn. • DIP/RBILD • Acute HP • Drug-induced ILD • chronic HP • Drug-induced injury • CVD-associated ILD • Asbestosis, Silicosis
  26. 26. Sarcoidosis
  27. 27. Histiocytosis X
  28. 28. Lymphangioleiomyomatosis
  29. 29. IPF
  30. 30. HRCT Confident CT diagnosis of IPF with consistent clinical features Atypical clinical or CT features for IPF TBBx or BAL? Features diagnostic of another DPLD e.g. HX If non-diagnostic Suspected other DPLD TBBx, BAL or other relevant test Surgical lung biopsy UIP NSIP RB DIP DAD OP LIP non-IIP confirmed
  31. 31. IPF without surgical biopsy (ATS/ERS Statement 2000) Major Criteria (all required) Minor criteria (3 of 4 required) • exclusion of known causes • age > 50 yr of ILD • insidious onset of otherwise • abnormal PFT including unexplained dsypnea on restriction and impaired exertion gas exchange • duration of illness > 3 • bibasilar reticular months abnormalities with minimal ground glass on HRCT • bibasilar inspiratory crackles • TBB or BAL showing no (velcro-type) features to support an alternate diagnosis
  32. 32. Idiopathic Pulmonary Fibrosis: typical CT features • Subpleural/basal • Fine reticular • Honeycombing • Little/no groundglass
  33. 33. HRCT Criteria of IPF 1-reticular abnormality and/or traction bronchiectasis with basal and peripheral predominance 2-honeycombing with basal and peripheral predominance 3-atypical features are absent – – – – Micronodules are not present peribronchovascular nodules are not present consolidation is not present ground glass attenuation, if present, is less extensive than reticular opacity – mediastinal adenopathy, if present, is not extensive enough to be visible on chest X-ray Definite IPF: all 3 are met Probable IPF: 1 and 3 are met
  34. 34. Accuracy of Clinical & Radiological Diagnosis of IPF • 59 patients with surgical biopsies • clinical diagnosis or radiological diagnosis • clinical diagnosis of IPF - 97% specific - 62% sensitive • HRCT diagnosis of IPF - 90% specific - 79% sensitive Raghu et al, 1999
  35. 35. Pitfalls with CT Technical Issues • HRCT vs. conventional CT • Gravity effects • Expiration
  36. 36. Conventional CT vs HRCT Conventional CT HRCT
  37. 37. IPF inverted Position
  38. 38. Bronchiolitis: Mosaic Pattern Inspiration Exspiration
  39. 39. Role of BAL in IPF • BAL may reveal alternative specific diagnoses: malignancy, infections, eosinophilic pneumonia, histiocytosis X, alveolar proteinosis • Increase in neutrophils +/eosinophils (in 90%) suggests a fibrosing process: IPF, collagen/vascular disease, asbestosis • A lone increase in lymphocytes is uncommon, exclude: sarcoidosis, EAA, BOOP, NSIP, LIP
  40. 40. HRCT Confident CT diagnosis of IPF with consistent clinical features Atypical clinical or CT features for IPF TBBx or BAL? Features diagnostic of another DPLD e.g. HX If non-diagnostic Suspected other DPLD TBBx, BAL or other relevant test Surgical lung biopsy UIP NSIP RB DIP DAD OP LIP non-IIP confirmed
  41. 41. When do we need surgical biopsy in idiopathic interstitial pneumonias? • IPF-like CT pattern and age > 50 yrs: no • COP with characteristic clinical/CT/BAL/TBLB features: no • RBILD/DIP? • Other IIP entities: yes
  42. 42. Surgical Lung Biopsy – special risk in IPF • 60 pat with UIP (46 idiopathic, 14 associated with collagen/vasc dis) from Mayo Clinic 1986 - 1995 • 10/60 (=17%) died within 30 days after surgical biopsy 3/16 (19%) after VATS 7/44 (16%) after thoracotomy and biopsy • All 10 who died had IPF, 5 of these were biopsied for accelerated progress Utz et al, ERJ 2001; 17: 175
  43. 43. Mortality and Risk factors for Surgical Lung Biopsy in IIP • 200 pat. with IIP (140 IPF, 46 NSIP, 14 COP), retrospective study • 4.3% died within 30 days after surgical biopsy, no difference between VATS or OLB no difference between IPF and other IIPs • Biopsy at time of acute exacerbation: mortality 29% vs 3% • DLCO<50%: mortality 11% vs 1.4% Park JH et al, Eur J Cardiothorac Surg 2007
  44. 44. Key histopathological features - UIP Pattern • Dense fibrosis and honeycombing • Fibroblastic foci prominent • Patchy, heterogeneous pattern • Subpleural, paraseptel distribution
  45. 45. UIP pattern Fibroblastic Foci Courtesy T.V. Colby
  46. 46. Nonspecific Interstitial Pneumonia (NSIP) Pattern • Preserved architecture, variable fibrosis and cellularity • Few fibroblastic foci • Temporally homogenous • Inconsistent distribution
  47. 47. Cellular NSIP
  48. 48. Desquamative Interstitial Pneumonia (DIP) Pattern • Intra-alveolar macrophage accumulation • No fibroblastic foci • Uniform involvement • Diffuse distribution
  49. 49. Pulmonologists’ Problems with Pathologists • No description of pattern-specific features • No final report of the pattern
  50. 50. How to make the diagnosis of an IIP entity? • Not by histology alone! • To define a disease as idiopathic, all known associated conditions and causes have to be excluded. • This cannot be done by the pathologist – none of the histologic patterns are specific for the idiopathic entities but also seen in associated conditions. • The final diagnosis can only be made in a clinical/radiologic/pathologic synopsis.
  51. 51. Controversy and Confusion with the term UIP • Clinicians have used the name of the histological patterns for the clinical diagnosis • Radiologists use the term UIP for the HR-CT pattern • What is UIP? - A histological (or CT/or BAL) pattern, not a clinical diagnosis • Is UIP the same as IPF? -- No! (Histological UIP pattern can be seen in other ILDs) • Why not call IPF “idiopathic UIP“?
  52. 52. Clinical conditions associated with UIP pattern • Idiopathic pulmonary fibrosis/crytogenic fibrosing alveolitis • Collagen vascular disease • Drug toxity • Chronic hypersensitivity pneumonitis • Asbestosis • Familial idopathic pulmonary fibrosis • Hermansky-Pudlak syndrom
  53. 53. Prognosis of Fibrotic Interstitial Pneumonia IIP vs CVD-IP (n = 362; IIP 269, CVD 93) Idiopathic UIP vs CVD-UIP v Idiopathic NSIP vs CVD-NS Park JH, et al. AJRCCM 2007; 175: 705
  54. 54. Clinical conditions associated with NSIP pattern • No detectable cause (idiopathic NSIP) • Collagen vascular disease • Hypersensitivity pneumonitis • Drug-induced pneumonitis • Infection • Immunodeficiency including HIV infection
  55. 55. Chronic bird fancier‘s lung: histopathological and clinical correlation Ohtani et al 2005 • BOOP • NSIP, cellular 2 5 recurrent episodes, good outcome • NSIP, fibrotic • UIP-like 8 11 insidious onset, unfavorable outcome Total n = 26
  56. 56. Controversy • Do NSIP and DIP reflect early stages of the IPF/UIP patients ? • Majority of researchers believe now that these three histologic patterns also reflect three different entities
  57. 57. DIP Initial 24 months later Ryu 2005
  58. 58. Controversies with RBILD/DIP • Should RBILD be included in the IIP„s? 100% are cigarette smokers, so a disease of known aetiology! • DIP is not exclusively seen in smokers, 15% are nonsmokers Ryu et al. Chest 2005,127:178
  59. 59. Is histopathology still the gold standard for diagnosis? Problems: • Sampling error • Interoberserver variation between histopathologists
  60. 60. Discordant Lobar Histology Lower lobe: UIP Middle lobe: NSIP
  61. 61. Histopathologic Variability: Survival Depends on the UIP Pattern NSIP (n=30) Cumulative proportion surviving Discordant UIP(n=28) Concordant UIP (n=51) Flaherty et al: AJRCCM, 2001 Years CP1047154-2
  62. 62. Is histopathology still the gold standard for diagnosis? Problems: • Sampling error • Interoberserver variation between histopathologists
  63. 63. Rating of κ scores agreement κ score • perfect > 0.8 • substantial 0.6 - 0.8 • moderate 0.4 - 0.6 • fair 0.2 - 0.4 • slight 0.0 - 0.2 • poor = 0.0 Landis JR, Koch GG. 1977
  64. 64. Interobserver variation between histopathologists   In a recent study, 133 biopsies were assessed by 10 experienced specialist histopathologists The interobserver agreement was barely clinically acceptable: Kappa coefficient of agreement only 0.4 Nicholson et al, Thorax 2004
  65. 65. Kappa coefficients of agreement between 10 pathologists (Nicholson 2004) Diagnosis Lobar diagnosis (n=98) Final diagnosis (n=48) UIP 0.40 0.49 NSIP 0.32 0.32 DIP 0.67 0.71 OP 0.59 0.67 EAA 0.39 0.35 Sarcoidosis 0.76 0.82 Overall 0.39 0.43
  66. 66. Ideal ILD doctor "Pulmo-radio-pathologist" Combining 3 brains in one head!
  67. 67. HRCT in the Idiopathic Interstitial Pneumonias
  68. 68. • A radiologist‟s view of the spectrum of IIPs • HRCT sketches of the IIPs • Issues: – “Added value” signs on HRCT – Observer variation – Overlap lung disease
  69. 69. Idiopathic interstitial pneumonias a perception / definition: “A group of disorders with a shifting histopathological classification, unclear clinical significance, and largely unmemorable imaging features.” E.G.Journeyman 2001
  70. 70. IIPs included in the current classification: • • • • • Usual interstitial pneumonia (UIP) Non-specific interstitial pneumonia (NSIP) Respiratory Bronchiolitis (RB-ILD) Desquamative interstitial pneumonia (DIP) Diffuse alveolar damage / Acute interstitial pneumonia (AIP) • Organizing pneumonia (OP) • Lymphoid interstitial pneumonia (LIP) International Consensus (ATS/ERS) Classification of Idiopathic Interstitial Pneumonias 2002
  71. 71. Organizing pneumonia
  72. 72. Respiratory Bronchiolitis-ILD
  73. 73. Lymphoid interstitial pneumonia
  74. 74. Acute interstitial pneumonia
  75. 75. UIP: HRCT appearances • Subpleural basal honeycombing – May be component of ground glass opacification and fine reticular elements – Volume loss and traction bronchiectasis – Enlarged mediastinal lymph nodes
  76. 76. UIP basal subpleural honeycombing* *not merely reticular pattern, check density within cystic air spaces
  77. 77. UIP sarcoid
  78. 78. Accelerated UIP 5 weeks later
  79. 79. Differential diagnosis for rapid development of widespread ground glass opacification in IPF: • • • • • Accelerated phase of the disease Supervening heart failure (oedema) Opportunistic infection Drug reaction – esp. novel drugs (Spurious – expiratory CT)
  80. 80. Added value features on “UIP HRCT” • Lung cancer – n.b. differential of mass-like TB • Pulmonary oedema • “Not UIP” – Hypersensitivity pneumonitis – Centrilobular emphysema / presbyteric lung
  81. 81. NSIP…
  82. 82. NSIP: initial reports of CT spectrum of findings: • Ground glass opacification with or without areas of consolidation • Linear opacities and reticular pattern, but honeycombing limited or absent • Lower zone predominance, may be subpleural predilection Park et al Radiology 1995;195:645 Hartman et al Radiology 2000;217:701
  83. 83. NSIP A fibrosing lung disease in which ground glass is predominant and honeycombing is minimal or absent, often with a peripheral basal distribution
  84. 84. Some history: • 1989: No histological difference between CFA and fibrosing alveolitis in systemic sclerosis1. • 1994: Fibrosing alveolitis associated with systemic sclerosis has a better prognosis than lone CFA2. • 1992/4: Kitaichi, Katzenstein describe NSIP • 1997: Chan et al paper in Thorax • 1998 – : Clinicians, radiologists recognize NSIP and its prognostic implications 1 Harrison et al Respir Med 1989;83:403-14 2 Wells et al Am J Respir Crit Care Med 1994;149:1583
  85. 85. “systemic sclerosis type” “lone CFA type” Chan et al. Thorax 1997;52:265 n.b. Subsequent pathological studies have shown that NSIP is the most prevalent pattern in systemic sclerosis associated pulmonary fibrosis
  86. 86. NSIP Gr 3 (fibrotic)
  87. 87. NSIP Gr 1 (cellular)
  88. 88. NSIP Hmmm……. UIP
  89. 89. NSIP with superimposed centrilobular emphysema
  90. 90. • Cigarette smoking • Ageing (presbyteric) lung “expected” changes
  91. 91. Cigarette smokers
  92. 92. 2x cigarette smokers (<65 years old)
  93. 93. 80 year old
  94. 94. 73 year old
  95. 95. If not UIP (n.b. non-typical HRCT UIP) consider: • • • • NSIP (fibrotic) Chronic hypersensitivity pneumonitis Fibrotic sarcoidosis Organizing pneumonia admixed fibrosis
  96. 96. UIP – The most frequently encountered and lethal IIP – Characteristic HRCT features in approximately 50% – Biopsy unnecessary when HRCT and clinical features typical NSIP – Better prognosis than UIP – Commonest IIP in connective tissue disease – HRCT pattern recognisable but not specific (may be a front for UIP)
  97. 97. Radiologists’ Observer Variation Thorax 2004;59:506
  98. 98. Interobserver variation between pathologists in diffuse parenchymal lung AG Nicholson, BJ Addis1, H Bharucha2, CA Clelland3, B Corrin, AR Gibbs4, PS Hasleton5, K Kerr6, NB Ibrahim7, S Stewart8, W Wallace9, and AU Wells10. Departments of Histopathology, Royal Brompton Hospital, Southampton General Hospital1, Royal Victoria Hospital, Belfast2, John Radcliffe Infirmary3, Llandough Hospital 4, Wythenshawe Hospital 5, Aberdeen Royal Hospitals6, Frenchay Hospital 7, Papworth Hospital 8, Edinburgh Royal Hospital9, and Department of Medicine10, Royal Brompton Hospital, UK. Thorax 2004;59:500
  99. 99. Kappa values for histopathological diagnosis [<0.4 = poor, 0.4-0.6 = satisfactory, 0.6-0.8 = good, >0.8 = excellent] Overall kappa value = 0.38 for lobar diagnoses DIAGNOSIS (n=133) KAPPA COEFFICIENT FOR LOBAR Dx UIP 0.42 NSIP 0.29 OP 0.57 Hypersensitivity pneumonitis 0.36 Sarcoidosis 0.76 Other diffuse lung diseases 0.41
  100. 100. “The only use of a diagnostic test is to reduce uncertainty” EJ Potchen 1998
  101. 101. Change in diagnostic perception: 1st choice diagnosis changed in 51% of cases after HRCT • Significant increase in diagnostic confidence • Overall kappa for 1st choice diagnosis before HRCT 0.47 (moderate) after HRCT 0.72 (good) Aziz et al Radiology 2006;238:725
  102. 102. Weighted kappa coefficients of individual disease categories for the entire cohort before and after HRCT Kw before HRCT Kw after HRCT Idiopathic pulmonary fibrosis 0.58 0.89 Non-specific interstitial pneumonitis 0.20 0.63 Sarcoidosis 0.68 0.88 Hypersensitivity pneumonitis 0.65 0.67 Cryptogenic organizing pneumonia 0.51 0.71 Smoking related-interstitial lung disease 0.30 0.46 Interstitial pneumonias secondary to connective tissue disease 0.69 0.78
  104. 104. When HRCT shows several patterns, it may be that: – Single disease has more than one HRCT pattern OR – More than one disease present OR – Two phases of one disease
  105. 105. Examples of coexistence: • Non-specific interstitial pneumonia (NSIP) - usual interstitial pneumonia (UIP) • Smoking related interstitial diseases – RB-ILD / NSIP / Langerhan’s / emphysema 2 1
  106. 106. Possible / probable transformations: • • • • • AIP → NSIP OP → NSIP / UIP? DIP → NSIP RBILD → emphysema? Normal → fibrosis / emphysema (aging)
  107. 107. • AIP – acute interstitial pneumonia • OP – organizing pneumonia • NSIP – non-specific interstitial pneumonia Clearly separated in the ATS/ERS classification
  108. 108. Defining features of Acute Interstitial Pneumonia (AIP) • Clinical: fulminant • Pathology: weeping lung (DAD) • Imaging: whiteout
  109. 109. Defining features of Organizing Pneumonia (OP) • Clinical: ~non-bacterial pneumonia • Pathology: loose granulation tissue • Imaging: multifocal consolidation
  110. 110. Defining features of Nonspecific Interstitial Pneumonia (NSIP) • Clinical: chronic indolent • Pathology: uniform fibrosis • Imaging: ground glass + distortion
  111. 111. So, AIP, OP and NSIP are very different entities…
  112. 112. Strands of evidence suggesting overlap between in situations in which AIP/NSIP/OP occur: • Dilated airways (irreversible) in gr. glass of ARDS (Howling et al 1998) • Original description of NSIP; some cases = ARDS survivors (Katzenstein et al 1994) • Variable behaviour of patients with polymyositis associated lung disease (Tazelaar et al 1990) • Accelerated phase of UIP/NSIP→AIP (Colby 2000) • HRCT descriptions of NSIP with consolidation (OP) (Park et al 1998)
  113. 113. 2000 2003 2005
  114. 114. Chest 2003;124:1185
  115. 115. HRCT and the Idiopathic Interstitial Pneumonias • Value – Some IIPs have diagnostic HRCT appearances – Alternative diagnoses + complications – Increased understanding of evolution • Limitations – NSIP masquerading as UIP – Clinical significance of limited disease – Experience / observer variation issues
  116. 116. Lung Cysts Differential Diagnosis Pulmonary fibrosis (Honeycombing) Lymphangliomyomatosis Langerhans cell histiocytosis Lymphocytic Interstitial Pneumonia (LIP)
  117. 117. UIP UIP or NSIP Traction Bronchiectasis and Interface sign Honey combing Rough Reticular Fine Reticular
  118. 118. Usual Interstitial Pneumonia UIP HRCT Findings Reticular opacities, thickened intra- and interlobular septa Irregular interfaces Honey combing and parenchymal distorsion Ground glass opacities (never prominent) Basal and subpleural predominance
  119. 119. Basal and subpleural distribution UIP
  120. 120. The Many ‘HRCT Faces’ of NSIP Honeycombing not a prominent feature !!!!
  121. 121. Lymphangioleiomyomatosis (LAM) HRCT Morphology Thin-walled cysts (2mm - 5cm) Uniform in size / rarely confluent Homogeneous distribution Chylous pleural effusion Lymphadenopathy in young women
  122. 122. Lymphangioleiomyomatosis (LAM)
  123. 123. Tuberous Sclerosis (young man)
  124. 124. Langerhans Cell Histiocytosis HRCT Findings Small peribronchiolar nodules (1-5mm) Thin-walled cysts (< 1cm), Bizarre and confluent Ground glass opacities Late signs: irreversible / parenchymal fibrosis Honey comb lung, septal thickening, bronchiectasis
  125. 125. Langerhans Cell Histiocytosis 1 year later Peribronchiolar Nodules Cavitating nodules and cysts
  126. 126. Langerhans Cell Histiocytosis
  127. 127. Langerhans Cell Histiozytosis Key Features Upper lobe predominance Combination of cysts and noduli Characteristic stages Increased Lung volume Sparing of costophrenic angle S M O K I N G
  128. 128. Langerhans Cell Histiocytosis
  129. 129. Langerhans Cell Histiocytosis Differential Diagnosis Only small nodules Sarcoidosis, Silicosis Only cysts idiopathic Fibrosis LAM Destructive emphysema
  130. 130. A professional diver..........
  131. 131. .......after cessation of smoki
  132. 132. LIP = Lymphocytic Interstitial Pneumonia Benign lymphoproliferative disorder Diffuse interstitial infiltration of mononuclear cells Not limited to the air ways as in follicular Bronchiolitis
  133. 133. Sjögren: LIP
  134. 134. LIP = Lymphocytic Interstitial Pneumonia Rarely idiopathic In association with: Sjögren‟s syndrome Immune deficiency syndromes, AIDS Primary biliary cirrhosis Multicentric Castlemean‟s disease
  135. 135. Sjoegren disease Dry eye and dry mouth Fibrosis, bronchitis and bronchiolitis LIP Up to 40 x increased risk for lymphoma (mediastinal adenopathy) and 2 x times increased risk for neoplasma Overlap Sarcoid, DM/PM, MXCT SLE, RA (pleural effusion)
  136. 136. Young woman LAM Dry mouth LIP Smoker Histiocytosis
  137. 137. Emphysema Fibrosis (UIP
  138. 138. Wegener„s disease
  139. 139. Rheumatoid Arthritis
  140. 140. Outline Typical HRCT patterns of lung diseases with cysts Mosaic pattern and its differential Emphysema Atypical HRCT patterns Quiz
  141. 141. Where is the pathology ??????? in the areas with increased density meaning there is ground glass in the areas with decreased density meaning there is air trapping
  142. 142. Pathology in black areas Airtrapping: Airway Disease Bronchiolitis obliterans (constrictive bronchiolitis) idiopathic, connective tissue diseases, drug reaction, after transplantation, after infection Hypersensitivity pneumonitis granulomatous inflammation of bronchiolar wall Sarcoidosis granulomatous inflammation of bronchiolar wall Asthma / Bronchiectasis / Airway diseases
  143. 143. Airway Disease what you see…… In inspiration sharply demarcated areas of seemingly increased density (normal) and decreased density demarcation by interlobular septa In expiration „black‟ areas remain in volume and density „white‟ areas decrease in volume and increase in density INCREASE IN CONTRAST DIFFERENCES AIRTRAPPING
  144. 144. Bronchiolitis obliterans
  145. 145. Early Sarcoidosis
  146. 146. Chronic EAA
  147. 147. Hypersensitivity pneumonitis Extr. Allerg. Alveolitis (EAA) HRCT Morphology acute - subacute acinar (centrilobular) unsharp densities ground glass (patchy - diffuse) chronic: fibrosis Intra- / interlobular septal thickening Irregular interfaces Traction bronchiectasis
  148. 148. Pathology in white Areas Alveolitis / Pneumonitis Ground glass desquamative intertitial pneumoinia (DIP) nonspecific interstitial pneumonia (NSIP) organizing pneumonia In expiration both areas (white and black) decrease in volume and increase in density DECREASE IN CONTRAST DIFFERENCES
  149. 149. DI P
  150. 150. Cellular NSIP
  151. 151. Mosaic Perfusion Chronic pulmonary embolism LOOK FOR Pulmonary hypertension idiopathic, cardiac disease, pulmonary disease
  152. 152. CTEPH = Chronic thrombembolic pulmonary hypertension
  153. 153. HRCT: Radiographic Pattern
  154. 154. Radiographic Patterns in ILD Pleural Involvement Lymphangitic Carcinomatosis LAM Drug Induced Radiation Pneumonitis Asbestosis Effusion Thickening Plaques Mesothelioma Collagen vascular disease Adenopathy Sarcoidosis Lymphoma Lymphangitic CA LIP Amyloidosis Berylliosis Silicosis Kerley B lines Chronic LV failure Lymphangitic CA Lymphoma LAM Veno-occlusive disease Acute Eosinophilic Pneumonia
  155. 155. Probability of Histologic Diagnosis of Diffuse Diseases Transbronchial Biopsy Surgical Biopsy 1. Granulomatous diseases 2. Malignant tumors/lymphangitic 3. DAD (any cause) 4. Certain infections Often 5. Alveolar proteinosis 6. Eosinophilic pneumonia 7. Vasculitis 8. Amyloidosis 9. EG/HX/PLCH Sometimes 10. LAM 11. RB/RBILD/DIP 12. UIP/NSIP/LIP COP 13. Small airways disease 14. PHT and PVOD Courtesy of Kevin O. Leslie, MD. Never
  156. 156. Practical Approach to Interstitial Lung Diseases
  157. 157. Patterns of Interstitial Lung Disease
  158. 158. Linear Pattern A linear pattern is seen when there is thickening of the interlobular septa, producing Kerley lines. Kerley A lines Kerley B lines Kerley A lines The interlobular septa contain pulmonary veins and lymphatics. The most common cause of interlobular septal thickening, producing Kerley A and B lines, is pulmonary edema, as a result of pulmonary venous hypertension and distension of the lymphatics. Kerley B lines
  159. 159. DD of Kerly Lines: Pulmonary edema is the most common cause Mitral stenosis Lymphangitic carcinomatosis Malignant lymphoma Congenital lymphangiectasia Idiopathic pulmonary fibrosis Pneumoconiosis Sarcoidosis
  160. 160. b. Reticular Pattern A reticular pattern results from the summation or superimposition of irregular linear opacities. The term reticular is defined as meshed, or in the form of a network. Reticular opacities can be described as fine, medium, or coarse, as the width of the opacities increases. A classic reticular pattern is seen with pulmonary fibrosis, in which multiple curvilinear opacities form small cystic spaces along the pleural margins and lung bases (honeycomb lung)
  161. 161. This 50-year-old man presented with end-stage lung fibrosis PA chest radiograph shows medium to coarse reticular B: CT scan shows multiple small cysts (honeycombing) involving predominantly the subpleural peripheral regions of lung. Traction bronchiectasis, another sign of end-stage lung fibrosis.
  162. 162. c. Nodular pattern  A nodular pattern consists of multiple round opacities, generally ranging in diameter from 1 mm to 1 cm  Nodular opacities may be described as miliary (1 to 2 mm, the size of millet seeds), small, medium, or large, as the diameter of the opacities increases  A nodular pattern, especially with predominant distribution, suggests a specific differential diagnosis
  163. 163. Disseminated histoplasmosis and nodular ILD. CT scan shows multiple bilateral round circumscribed pulmonary nodules.
  164. 164. Hematogenous metastases and nodular ILD. This 45-yearold woman presented with metastatic gastric carcinoma. The PA chest radiograph shows a diffuse pattern of nodules, 6 to 10 mm in diameter.
  165. 165. Differential diagnosis of a nodular pattern of interstitial lung disease SHRIMP Sarcoidosis Histiocytosis (Langerhan cell histiocytosis) Hypersensitivity pneumonitis Rheumatoid nodules Infection (mycobacterial, fungal, viral) Metastases, Miliary TB Microlithiasis, alveolar Pneumoconioses (silicosis, coal worker's, berylliosis)
  166. 166. d. Reticulonodular pattern A reticulonodular pattern results from a combination of reticular and nodular opacities. This pattern is often difficult to distinguish from a purely reticular or nodular pattern, and in such a case a differential diagnosis should be developed based on the predominant pattern. If there is no predominant pattern, causes of both nodular and reticular patterns should be considered.
  167. 167. How To Approach a Practical Diagnosis?
  168. 168. Rule no. 1 An acute appearance suggests pulmonary edema, acute milliary TB, or acute interstitial neumonia,acute esinophillic pneumonia
  169. 169. Disseminated histoplasmosis and reticulonodular ILD. A: PA chest radiograph, close-up of right upper lung, shows reticulonodular ILD. B: CT scan shows multiple circumscribed round pulmonary nodules, 2 to 3 mm in diameter.
  170. 170. Rule no. 2 Reticulonodular lower lung predominant distribution with decreased lung volumes suggests: (APC) 1. Asbestosis 2. Aspiration (chronic) 3. Pulmonary fibrosis (idiopathic) 4.Collagen vascular disease
  171. 171. Asbestos-related pleural disease and asbestosis
  172. 172. Pulmonary fibrosis and rheumatoid arthritis.
  173. 173. Systemic sclerosis. A: PA chest radiograph shows a bibasilar and subpleural distribution of fine reticular ILD. The presence of a dilated esophagus (arrows) provides a clue to the correct diagnosis. B: CT scan shows peripheral ILD and a dilated esophagus (arrow).
  174. 174. Rule no. 3 A middle or upper lung predominant distribution suggests: (Mycobacterium Settle Superiorly in Lung) 1. Mycobacterial or fungal disease 2. Silicosis 3. Sarcoidosis 4. Langerhans Cell Histiocytosis
  175. 175. Complicated silicosis. PA chest radiograph shows multiple nodules involving the upper and middle lungs, with coalescence of nodules in the left upper lobe resulting in early progressive massive fibrosis
  176. 176. Sarcoidosis. CT scan shows nodular thickening of the bronchovascular bundles (solid arrow) and subpleural nodules (dashed arrow), illustrating the typical perilymphatic distribution of sarcoidosis.
  177. 177. Langerhan cell histiocytosis. This 50-year-old man had a 30 pack-year history of cigarette smoking. A: PA chest radiograph shows hyperinflation of the lungs and fine bilateral reticular ILD. B: CT scan shows multiple cysts (solid arrow) and nodules (dashed arrow).
  178. 178. Rule no. 4 Associated lymphadenopathy suggests : 1.Sarcoidosis-Berryliosis 2.neoplasm (lymphangitic carcinomatosis, lymphoma, metastases) 3. infection (viral, mycobacterial, or fungal) 4. silicosis
  179. 179. Simple silicosis. A: CT scan with lung windowing shows numerous circumscribed pulmonary nodules, 2 to 3 mm in diameter (arrows). B: CT scan with mediastinal windowing shows densely calcified hilar (solid arrows) and subcarinal (dashed arrow) nodes.
  180. 180. Rule no. 5 Associated pleural thickening and/or calcification suggest asbestosis.
  181. 181. Rule no. 6 Associated pleural effusion suggests : 1.pulmonary edema 2.lymphangitic carcinomatosis 3.lymphoma 4.collagen vascular disease 5.LAM
  182. 182. Cardiogenic pulmonary edema. PA chest radiograph shows enlargement of the cardiac silhouette, bilateral ILD, enlargement of the azygos vein (solid arrow), and peribronchial cuffing (dashed arrow).
  183. 183. Lymphangitic carcinomatosis. This 53-year-old man presented with chronic obstructive pulmonary disease and large-cell bronchogenic carcinoma of the right lung. CT scan shows unilateral nodular thickening (arrows) and a malignant right pleural effusion.
  184. 184. Rule no. 7 Associated pneumothorax suggests lymphangioleiomyomatosis or LCH.
  185. 185. Lymphangioleiomyomatosis (LAM). A: PA chest radiograph shows a right basilar pneumothorax and two right pleural drainage catheters. The lung volumes are increased, which is characteristic of LAM, and there is diffuse reticular ILD. B: CT scan shows bilateral thinwalled cysts and a loculated right pneumothorax (P).
  186. 186. A p p ro a c h to th e IL D P a tie n t P a tie n t w ith S u sp e c te d IL D H x, P E , C X R , P F T , L a b s D x lik e ly b y b ro n c h ? Y es Y es Is b ro n ch d ia g n o stic? No STO P HRCT H x and H R C T co n siste n t w ith IP F H x and H R C T D x o f o th e r IL D S u sp e cte d o th e r IL D STOP D x lik e ly b y b ro n c h ? STOP A typ ica l clin ica l o r C T fe a tu re s o f IP F Y es Is b ro n ch d ia g n o stic? No No Y es STO P VATS U IP N S IP R B IL D D IP DAD OP L IP N o n IIP M a rtine z F , F la h erty K . A va ila ble a t: h ttp ://w w w .ch e stn e t.o rg /e d u ca tion /onlin e /p ccu /vol1 8 /lesso n s03 _ 04 /le sso n 03 .p hp .